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Omega-3 and -6 Fatty Acids, Plasma

Test code(s) 91001

The FAQ information attached by the previously provided link was retired on 8/18/2015. The link continues to be available for your historic reference. Current FAQs can be viewed at QuestDiagnostics.com/FAQs

Question 1. What is the clinical significance of the EPA/AA ratio?

High levels of eicosapentaenoic acid (EPA) and low levels of arachidonic acid (AA) are associated with fewer CVD events.

  • In the JELIS investigation, a plasma EPA/AA ratio >0.75 was associated with a significantly reduced risk for coronary events.1
  • In 1,050 patients with a prior myocardial infarction (MI), supplementation with 1,800 mg/day EPA increased the EPA/AA ratio from 0.6 to 1.3.2 Those patients who achieved an EPA/AA ratio ≥1.06, compared to those with an EPA/AA ≤0.55, had a significant reduction in cardiac death and MI.2

Question 2. How were the risk cut points for the omega-3 index determined?

Multiple studies of patients who were either at risk of cardiovascular disease (CVD) or who had had a non-fatal MI showed that individuals with the highest omega-3 levels (typically the highest quartile) are at reduced risk of CVD events, compared with those in lowest omega-3 quartile. In the Physicians’ Health Study, higher blood levels of EPA+DHA+DSA, as a percent of total fatty acids, were associated with a significant reduction (p=0.007) in sudden death from cardiac causes after adjustment for potential confounders.3

The risk cut points used in our plasma-based omega-3 index test are based on quartiles determined by our testing of samples from apparently healthy adults. Plasma phospholipid omega-3 index levels in the bottom quartile (<1.1%) are classified as high risk; the central 2 quartiles (1.1% to 3.3%) as moderate risk, and the highest quartile (>3.3%) as low risk.

Question 3. What sample type and collection conditions are required for the plasma omega-3 and omega-6 fatty acid test (test code 91001)?

The patient should be fasting for 8 to 12 hours before the sample collection. Collect sample in lavender-top (EDTA) tube and separate the plasma from the cells. Ship 2.0 mL (0.4 mL minimum) of EDTA plasma at ambient temperature, refrigerated, or frozen.

Question 4. What effect can fish oil supplementation have on advanced lipoprotein measurements?

Omega-3 supplementation has been reported to significantly improve the lipoprotein profile: specifically, it substantially increased HDL2b and LDL peak particle size.4

Question 5. What is the difference between plasma-based and RBC membrane-based methods for measuring fatty acids?

In both methods, fatty acids are identified by comparison with known standards, and their composition is reported as weight percent of total phospholipid fatty acids. The sum of EPA plus DHA, as a percentage of total phospholipid fatty acids measured, is reported as the omega-3 index.

The Quest Diagnostics test is plasma-based and determines the fatty acid concentration in plasma phospholipids using a liquid chromatography, tandem mass spectrometry (LC/MS/MS) method. Phospholipids are extracted and hydrolyzed before LC/MS/MS analysis. Since this plasma-based method may be influenced by recent diet or supplement use, we recommend patients be in a fasting state when samples are collected.

In an RBC-based method, fatty acids from red blood cell phospholipids are hydrolyzed, esterified, extracted with hexane, and analyzed by flame ionization gas chromatography.

Question 6. What is the clinical difference between results obtained using the Quest Diagnostics plasma-based method versus the RBC-based method?

With either method, a higher omega-3 index is associated with decreased cardiovascular disease risk.

The plasma-based method has been used in multiple studies. A plasma EPA concentration ≥150 µg/mL (compared to <87 µg/mL) was associated with a significant 20% reduction in major coronary events in 15,534 subjects in the JELIS investigation.1

RBC-based methods have also been used in several clinical trials. In these studies, patients with a high omega-3 index were atlow risk of acute coronary syndrome, while those with medium levels were at intermediate risk and those with low levels were at high risk, all relative to controls.5


  1. Itakura H, et al. J Atheroscler Thromb. 2011;18:99-107.
  2. Matsuzaki M, et al. Circ J. 2009;73:1283-1290.
  3. Albert CM, et al. N Engl J Med. 2002;346:1113-1118.
  4. Wooten JS, et al. J Appl Physiol. 2009;107:794-800.
  5. Block RC, et al. Atherosclerosis. 2008;197:821-828.
  6. Glaser C, et al. Metabolism. 2010;59:993-999.
  7. Lu Y, et al. Am J Clin Nutr. 2010;92:258-265.
  8. Martinelli N, et al. Am J Clin Nutr. 2008;88:941-949.
  9. Pottala JV, et al. Circ Cardiovasc Qual Outcomes. 2010;3:406-412.
  10. Raatz SK, et al. J Am Diet Assoc. 2009;109:1076-1081.
This FAQ is provided for informational purposes only and is not intended as medical advice. A clinician’s test selection and interpretation, diagnosis, and patient management decisions should be based on his/her education, clinical expertise, and assessment of the patient.
Document FAQS.67 Version: 1
Version 1 effective 06/20/2014 to 8/18/2015